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Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.
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Carcinoma de Células de Transição , Ácidos Nucleicos Livres , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Prognóstico , Biomarcadores , Biópsia LíquidaRESUMO
Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different follow-up time points. Two specific mutations (TERT c.1-124C>T and ATM c.1236-2A>T) were analyzed in the patients' plasma samples by droplet digital PCR to determine their ctDNA status. During a median follow-up of 21 months, 24% of patients progressed in a median of six months. ctDNA status was identified as a prognostic biomarker of tumor progression before RC and 4 and 12 months later (HR 6.774, HR 3.673, and HR 30.865, respectively; p < 0.05). Lastly, dynamic changes in ctDNA status between baseline and four months later were significantly associated with patient outcomes (p = 0.045). In conclusion, longitudinal ctDNA analysis using a tumor-agnostic approach is a potential tool for monitoring MIBC patients after RC. The implementation of this testing in a clinical setting could improve disease management and patients' outcomes.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Humanos , DNA Tumoral Circulante/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , DNA de Neoplasias , Biomarcadores , Músculos/patologia , Biomarcadores Tumorais/genética , MutaçãoRESUMO
Background and aims: The spatial and temporal genetic heterogeneity of bladder cancer (BC) makes challenging to find specific drivers of metastatic disease, thus preventing to determine those BC patients at high risk of tumor progression. Our aim was to identify DNA mutations providing aggressive behavior to bladder tumors and analyze them in patients' cell-free DNA (cfDNA) during their follow-up after radical cystectomy (RC) in order to monitor tumor evolution. Methods: Six BC patients who underwent RC and presented disease progression during their follow-up were included. Next-generation sequencing was used to determine somatic mutations in several primary tumor and metastatic specimens from each patient. Shared DNA mutations between primary bladder tumor and metastatic sites were identified in cfDNA samples through droplet digital PCR. Results: Besides BC genetic heterogeneity, specific mutations in at least one of these genes -TERT, ATM, RB1, and FGFR3- were found in primary tumors and their metastases in all patients. These mutations were also identified in the patients' cfDNA at different follow-up time points. Additionally, the dynamic changes of these mutations in cfDNA allowed us to determine tumor evolution in response to treatment. Conclusion: The analysis of BC mutations associated with poor prognosis in plasma cfDNA could be a valuable tool to monitor tumor evolution, thus improving the clinical management of BC patients.
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PURPOSE: The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivo dosimetry. The transit images acquired during each fraction can be compared with a predicted image, if available, or with a baseline image, usually the obtained in the first fraction. This work aims to study the dosimetric impact of the failing fractions and to evaluate the appropriateness of using a baseline image in breast plans. MATERIAL AND METHODS: Twenty breast patients treated in a Halcyon were retrospectively selected. For each patient and fraction, the treatment plan was calculated over the daily CBCT image. For each fraction, the differences respect to the treatment plan values of OARs and PTV dosimetric parameters were analyzed: ΔDmean , ΔD95%, ΔD98%, ΔD2%, ΔV36Gy, ΔV38.5Gy, and ΔV43.5Gy. Daily fractions were ranked according to the differences found in the dosimetric parameters between the treatment plan and the daily CBCT to establish the best fraction. The daily transit images acquired in every fraction were compared to the first fraction using the global gamma index with the Portal Dosimetry tool. The comparison was repeated using the best fraction image as a baseline. We assessed the correlation of the dosimetric differences obtained from the CBCT images-based treatment plans with the gamma index passing rates obtained using first fraction and best fraction as baseline. RESULTS: Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%] for the ∆PTVD98% and ∆PTVD95% per every 10% decrease in the passing rate were found, respectively. When using the best fraction as baseline patients were detected with failing fractions that were not detected with the first fraction as baseline. CONCLUSION: The gamma passing rates of daily transit images correlate with the coverage loss parameters in breast IMRT plans. Using first fraction image as baseline can lead to the non-detectability of failing fractions.
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Neoplasias da Mama , Radioterapia de Intensidade Modulada , Humanos , Feminino , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Mama/radioterapia , Estudos Retrospectivos , Radiometria/métodosRESUMO
Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Biomarcadores , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Humanos , Músculos/patologia , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
The inaccuracy of the current prognostic algorithms and the potential changes in the therapeutic management of localized ccRCC demands the development of an improved prognostic model for these patients. To this end, we analyzed whole-transcriptome profiling of 26 tissue samples from progressive and non-progressive ccRCCs using Illumina Hi-seq 4000. Differentially expressed genes (DEG) were intersected with the RNA-sequencing data from the TCGA. The overlapping genes were used for further analysis. A total of 132 genes were found to be prognosis-related genes. LASSO regression enabled the development of the best prognostic six-gene panel. Cox regression analyses were performed to identify independent clinical prognostic parameters to construct a combined nomogram which includes the expression of CERCAM, MIA2, HS6ST2, ONECUT2, SOX12, TMEM132A, pT stage, tumor size and ISUP grade. A risk score generated using this model effectively stratified patients at higher risk of disease progression (HR 10.79; p < 0.001) and cancer-specific death (HR 19.27; p < 0.001). It correlated with the clinicopathological variables, enabling us to discriminate a subset of patients at higher risk of progression within the Stage, Size, Grade and Necrosis score (SSIGN) risk groups, pT and ISUP grade. In summary, a gene expression-based prognostic signature was successfully developed providing a more precise assessment of the individual risk of progression.
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PURPOSE: Current clinical prognostic factors are not accurate enough to identify and monitor those muscle-invasive bladder cancer (MIBC) patients at high risk of progression after radical cystectomy (RC). Here, we determined genetic alterations in the tumor and circulating tumor cell (CTC) enumeration to find biomarkers useful for the management of MIBC after RC. METHODS: Thirty-nine MIBC patients undergoing RC were included. Tumoral tissue DNA was analyzed by next generation sequencing. CTCs were isolated from blood collected before RC and one, four and 12 months later. RESULTS: Sixteen (41%) patients progressed in a median time of 8.5 months and 11 (69%) of these patients harbored the TERT c.-124C > T mutation. All progressive patients harboring the TERT c.-124C > T mutation presented a significant increase in CTC number 12 months after RC compared to those without the mutation. Additionally, CTC number at 12 months was identified as an independent prognostic biomarker for tumor progression and cancer specific survival (CSS). Ten (63%) progressive patients showed an increment of CTC number with a median anticipation period of four months compared with imaging techniques. CONCLUSIONS: The TERT c.-124C > T mutation could be considered a biomarker of aggressivity. CTC enumeration is a useful tool for identifying MIBC patients at high risk of progression and CSS after RC and for detecting tumor progression earlier than imaging techniques.
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Células Neoplásicas Circulantes , Telomerase , Neoplasias da Bexiga Urinária , Biomarcadores , Cistectomia/métodos , Humanos , Músculos , Mutação , Invasividade Neoplásica , Prognóstico , Regiões Promotoras Genéticas , Telomerase/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
The probability of tumor progression in intermediate/high-risk clear cell renal cell carcinoma (ccRCC) is highly variable, underlining the lack of predictive accuracy of the current clinicopathological factors. To develop an accurate prognostic classifier for these patients, we analyzed global gene expression patterns in 13 tissue samples from progressive and non-progressive ccRCC using Illumina Hi-seq 4000. Expression levels of 22 selected differentially expressed genes (DEG) were assessed by nCounter analysis in an independent series of 71 ccRCCs. A clinicopathological-molecular model for predicting tumor progression was developed and in silico validated in a total of 202 ccRCC patients using the TCGA cohort. A total of 1202 DEGs were found between progressive and non-progressive intermediate/high-risk ccRCC in RNAseq analysis, and seven of the 22 DEGs selected were validated by nCounter. Expression of HS6ST2, pT stage, tumor size, and ISUP grade were found to be independent prognostic factors for tumor progression. A risk score generated using these variables was able to distinguish patients at higher risk of tumor progression (HR 7.27; p < 0.001), consistent with the results obtained from the TCGA cohort (HR 2.74; p < 0.002). In summary, a combined prognostic algorithm was successfully developed and validated. This model may aid physicians to select high-risk patients for adjuvant therapy.
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This study aimed to ascertain gene expression profile differences between progressive muscle-invasive bladder cancer (MIBC) and de novo MIBC, and to identify prognostic biomarkers to improve patients' treatment. Retrospective multicenter study in which 212 MIBC patients who underwent radical cystectomy between 2000 and 2019 were included. Gene expression profiles were determined in 26 samples using Illumina microarrays. The expression levels of 94 genes were studied by quantitative PCR in an independent set of 186 MIBC patients. In a median follow-up of 16 months, 46.7% patients developed tumor progression after cystectomy. In our series, progressive MIBC patients show a worse tumor progression (p = 0.024) and cancer-specific survival (CSS) (p = 0.049) than the de novo group. A total of 480 genes were found to be differently expressed between both groups. Differential expression of 24 out of the 94 selected genes was found in an independent cohort. RBPMC2 and DSC3 were found as independent prognostic biomarkers of tumor progression and CALD1 and LCOR were identified as prognostic biomarkers of CSS between both groups. In conclusion, progressive and de novo MIBC patients show different clinical outcome and gene expression profiles. Gene expression patterns may contribute to predict high-risk of progression to distant metastasis or CSS.
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Biomarcadores Tumorais/metabolismo , Cistectomia/métodos , Neoplasias Musculares/patologia , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Transcriptoma , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
Resumen: Objetivo: Caracterizar la necesidad de tratamiento ortodóntico en su componente de salud dental y estético en escolares de 11 a 12 años de la Institución Educativa Mariscal Gamarra del Cusco - Perú, 2019. Materiales y métodos: La muestra estuvo constituida por 142 escolares de una institución educativa estatal, se usó el Índice de Necesidad de Tratamiento Ortodóntico (INTO) con sus dos componentes. El Componente de Salud Dental (CDS) es realizado por el Odontólogo y el Componente Estético (CE) es percibido por el paciente. Resultados: Se obtuvo 15,49% sin necesidad de tratamiento y 33.10% de leve necesidad de tratamiento y 28,87% moderada necesidad de tratamiento en su Componente de Salud Dental y el 74,65% se presentó sin necesidad de tratamiento en su Componente Estético. Conclusión: Al examen por parte del profesional casi la mitad de los estudiantes no necesitan tratamiento y por otro lado, tres de cuatro estudiantes se perciben sin necesidad de tratamiento de ortodoncia.
Resumo: Objetivo: Caracterizar a necessidade de tratamento ortodôntico em seu componente de saúde dental e estética em escolares de 11 a 12 anos de idade na Instituição Educacional Mariscal Gamarra de Cusco - Peru, 2019. Materiais e métodos: A amostra foi composta por 142 estudantes de uma instituição de ensino estadual, o Índice de Necessidades de Tratamento Ortodôntico (INTO), com seus dois componentes. O componente de saúde bucal (CDS) é realizado pelo dentista e o componente estético (CE) é percebido pelo paciente. Resultados: foram obtidos 15,49% sem necessidade de tratamento e 33,10% para uma leve necessidade de tratamento e 28,87% para uma necessidade moderada de tratamento em seu Componente de Saúde Bucal e 74,65% apresentaram sem a necessidade de tratamento em seu Componente Estético. Conclusão: No exame realizado pelo profissional, quase metade dos estudantes não necessita de tratamento e, por outro lado, três em cada quatro percebem a si mesmos sem a necessidade de tratamento ortodôntico.
Abstract: Objective: To describe the need for orthodontic treatment in its dental and aesthetic health components in schoolchildren aged 11 to 12 at the Mariscal Gamarra Educational Institution of Cusco - Peru, 2019. Materials and methods: The sample consisted of 142 schoolchildren from a public school. The Index of Orthodontic Treatment Need (IOTN) was used with the two components; the Dental Health Component, determined by the dentist, and the Aesthetic Component, as perceived by the patient. Results: According to the results, 15.49% did not need any treatment, 33.10% had a slight need for treatment, and 28.87% a moderate need for treatment in the Dental Health component; 74.65% presented no need for treatment in the Aesthetic Component. Conclusion: Almost half the students did not need any treatment as reported after the health professional exam. On the other hand, three out of four students showed no need for orthodontic treatment.
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Humanos , Criança , Peru , Criança , Índice de Necessidade de Tratamento Ortodôntico , Estética Dentária , Má OclusãoRESUMO
Light-sticks are used as bait in surface long-line fishing, to capture swordfish and other large pelagic predators. When discharged in the ocean, it may reach the beaches. The traditional Brazilian community of Costa dos Coqueiros, Bahia, use light-sticks as a medicine for rheumatism, vitiligo and mycoses. It may affect the marine life when its content leak in the open ocean. This work evaluated and identified the acute and chronic toxicity of the light-stick. A high acute toxicity was observed in the mobility/mortality of Artemia sp.; in the fertilization of sea urchin eggs, and a high chronic toxicity in the development of the pluteus larvae of the same sea urchin. The main compounds that probably caused toxicity were the volatiles such as the fluorescent PAH and oxidants such as the hydrogen peroxide. Its disposal in the open ocean is a potential threat for marine life.
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Artemia , Poluição Ambiental , Ouriços-do-Mar , Poluentes Químicos da Água/toxicidade , Animais , Brasil , Oxidantes/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Testes de ToxicidadeAssuntos
Abscesso Encefálico/diagnóstico , Coinfecção/diagnóstico , Hospedeiro Imunocomprometido , Transplante de Rim , Nocardiose/diagnóstico , Infecções Oportunistas/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Idoso , Abscesso Encefálico/imunologia , Coinfecção/imunologia , Corpo Caloso/microbiologia , Evolução Fatal , Humanos , Imunossupressores/efeitos adversos , Masculino , Nocardiose/imunologia , Infecções Oportunistas/imunologia , Complicações Pós-Operatórias/imunologiaRESUMO
Necrotizing fasciitis is a severe infection of the subcutaneous tissue, with a higher mortality if treatment is not adequate. Nursing care can be fundamental in obtaining a good outcome of the healing process. We present a case of an 80 year-old diabetic patient admitted to our orthopaedic surgery unit as consequence of a screw displacement in her hip. She was operated on and had to be immobilized during the postsurgical period. Measures were applied to prevent bed sores in the sacral region. Despite these measures the patient developed a pressure sore that became infected, progressing to a necrotizing fasciitis of perineal and bulbar region, which required surgical curettage. Due to contact and exposure to faecal material it was decided to use a faecal shunt system. The number and difficulty of the wound treatments decreased using this system, which had significant advantages for the patient and nurses and for a favourable outcome of the wound. Employing faecal shunt systems could be useful when they are used earlier in patients immobilized due to orthopaedic surgery, with bowel movement changes and bed sore wounds.
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Fasciite Necrosante/cirurgia , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Fezes , Feminino , Unidades Hospitalares , Humanos , Ortopedia , PeríneoRESUMO
Preocupada por la alta frecuencia de quemaduras en niños producidas por el uso de fuegos artificiales durante las fiestas de navidad y año nuevo, la Corporación de Ayuda al Niño Quemado, Coaniquem, en asociación con el Ministerio de Salud, efectuó desde 1993 una campaña de prevención junto con una vigilancia epidemiológica de este accidente que se hizo extensiva a todo el país en 1997. Dicha campaña tuvo un leve efecto en su objetivo principal pero logró concientizar a la opinión pública sobre la importancia del problema y convenció a las autoridades sobre la conveniencia de modificar drásticamente la legislación que regula la fabricación y venta de estos productos. Habiéndose dictado una nueva ley que prohibió, en el año 2000, la venta de fuegos artificiales para uso personal en Chile, se quiso conocer el impacto de la medida para lo cual se comparó la incidencia de quemaduras infantiles ocurridas en las fiestas de fin de año, registradas a través de la vigilancia epidemiológica, de los tres años previos al cambio con los tres años posteriores a éste. Se observó una disminución de 85 por ciento en el número de casos y de un 3,8 por ciento de las hospitalizaciones. No hubo cambios en los fuegos artificiales usados ni en las localizaciones de las lesiones. La tenencia de los fuegos artificiales sólo pudo explicarse como consecuencia de comercio clandestino en todos los casos. La prohibición ha resultado muy efectiva, pero la venta ilegal obliga a continuar la campaña preventiva y efectuar una estricta fiscalización del cumplimiento de la ley.
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Humanos , Pré-Escolar , Criança , Promoção da Saúde , Legislação , Queimaduras/epidemiologia , Queimaduras/prevenção & controle , Prevenção de Acidentes , Chile , Queimaduras/mortalidadeAssuntos
Humanos , Masculino , Feminino , Mão de Obra em Saúde , Ocupações em Saúde , Médicos , Educação ContinuadaRESUMO
Se realiza un estudio de campo con 116 nños de 4 meses, vacunados al nacer con la vacuna BCG Liofilizada del Instituto Rhodia Merieux, importada de Francia y sometida a control de calidad por el Instituto de Salud Pública de Chile. En el presente trabajo se empleó el mismo método y observadores que en un trabajo anterior sobre la vacuna BCG Liofilizada de Laboratorios Connaught (Canadá). La vacuna en estudio deja una cicatriz semejante a las utilizadas anteriormente en Chile; la respuesta Tuberculínica es débil: media 4,8 mm. D.S. 3,5mm., y se encontró una diferencia significativa al compararla con la vacuna BCG Líquida fabricada por el Instituto de Salud Pública de Chile la que aparece dando una mucho mejor respuesta tuberculínica (p = <0.001). Al comparar las dos vacunas BCG Liofilizadas, no se advierten diferencias importantes, demostrándose ambas considerablemente más débiles en su respuesta tuberculínica que la vacuna BCG Líquida. Los controles de calidad "in vitro" de la vacuna BCG Liofilizada del Instituto Rhodia Merieux demostraron que se estable y promisoria desde el punto de vista operacional